Although melatonin has been established as a free radical scavenger and antioxidant, its effects in diabetes have not been thoroughly investigated. The purpose of this study, therefore, was to investigate the effects of melatonin administration on lipid peroxidation and antioxidant status in streptozotocin (STZ)-induced diabetes in rats. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) in erythrocytes and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were compared in 3 groups of 10 rats each [control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)]. In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60-mg/kg dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10-mg/kg i.p. dose of melatonin per day. After 6 wk, the rats in groups II and III had significantly lower body weights and significantly higher blood glucose levels than the rats of group I (P<0.001 and P<0.001, respectively). There were no significant differences in body weight or blood glucose levels between groups II and III. MDA levels in untreated diabetic rats were higher than those in control group rats and in diabetic rats treated with melatonin (P<0.01 and P<0.05, respectively). However, MDA levels in diabetic rats treated with melatonin were not different from those of the control group. The GSH, GSH-Px and SOD levels of untreated diabetic rats were significantly lower than those of the control group (P<0.02, P<0.002 and P<0.05, respectively). In group III, however, melatonin prevented decreases in the thiol antioxidant and the associated enzymes, and so these levels were not significantly different from those in the control group. These results confirm the presence of oxidative stress in STZ-induced experimental diabetes and indicate the beneficial free radical-scavenging and antioxidant properties of melatonin.

Potassium (K+) ion channel activity is an important determinant of vascular tone by regulating cell membrane potential (MP). Activation of K+ channels leads to membrane hyperpolarization and subsequently vasodilatation, while inhibition of the channels causes membrane depolarization and then vasoconstriction. So far five distinct types of K+ channels have been identified in vascular smooth muscle cells (VSMCs): Ca+2‐activated K+ channels (BKCa), voltage‐dependent K+ channels (KV), ATP‐sensitive K+ channels (KATP), inward rectifier K+ channels (Kir), and tandem two‐pore K+ channels (K2P). The activity and expression of vascular K+ channels are changed during major vascular diseases such as hypertension, pulmonary hypertension, hypercholesterolemia, atherosclerosis, and diabetes mellitus. The defective function of K+ channels is commonly associated with impaired vascular responses and is likely to become as a result of changes in K+ channels during vascular diseases. Increased K+ channel function and expression may also help to compensate for increased abnormal vascular tone. There are many pharmacological and genotypic studies which were carried out on the subtypes of K+ channels expressed in variable amounts in different vascular beds. Modulation of K+ channel activity by molecular approaches and selective drug development may be a novel treatment modality for vascular dysfunction in the future. This review presents the basic properties, physiological functions, pathophysiological, and pharmacological roles of the five major classes of K+ channels that have been determined in VSMCs.

The present investigation was designed to determine the protective effects of melatonin against bleomycin (BLM)-induced oxidant lung toxicity. Wistar-albino rats were divided into four groups: saline (SA, 0.4 mL/animal), 1% ethanol-saline (ALC, 0.4 mL/animal), bleomycin sulphate (BLM, 10 mg/kg), or bleomycin sulphate + melatonin (BLM, 10 mg/kg + MLT, 10 mg/kg). All injections were given intraperitoneally (i.p.), twice weekly for a period of 3 wk (a total of seven injections for each group). Twenty-five days after BLM treatment, pulmonary fibrosis was assessed as hydroxyproline content in lung homogenates. Findings show that BLM-induced pulmonary injury resulted in increases in bronchoalveolar lavage fluid (BALF) biomarkers including total protein, lactate dehydrogenase (LDH), glutathione-peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT). Additionally, the levels of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation (LPO), were also increased in BALF. Conversely, the level of glutathione (GSH) was reduced in BALF of BLM-treated rats. Melatonin provided protection against BLM-induced pulmonary fibrosis by suppressing oxidative stress. It abolished BLM-stimulated LPO and reversed the imbalance between oxidants and antioxidants in the BALFs. Results thus indicate that melatonin inhibits BLM-induced lung toxicity associated with oxidative damage.

Studies have shown that ischemia-reperfusion (I/R) produces free radicals leading to lipid peroxidation and to damage of the nervous tissue. Melatonin, a main secretory product of the pineal gland, has free radical scavenging and antioxidant properties and has been shown to diminish I/R injury in many tissues. There are a limited number of studies related to the effects of melatonin on I/R injury in the peripheral nervous system. Therefore, in the present study, the protective effect of melatonin was investigated in rats subjected to 2 hr of sciatic nerve ischemia followed by 3 hr of reperfusion. Following reperfusion, nerve tissue samples were collected for quantitative assessment of malondialdehyde (MDA), an oxidative stress marker, and superoxide dismutase (SOD), a principal antioxidant enzyme. Samples were further evaluated at electron microscopic level to examine the neuropathological changes. I/R elevated the concentration of MDA significantly while there was a reduction at SOD levels. Melatonin treatment reversed the I/R-induced increase and decrease in MDA and SOD levels, respectively. Furthermore, melatonin salvaged the nerve fibers from ischemic degeneration. Histopathologic findings in the samples of melatonin-treated animals indicated less edema and less damage to the myelin sheaths and axons than those observed in the control samples. Our results suggest that administration of melatonin protects the sciatic nerve from I/R injury, which may be attributed to its antioxidant property.

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